Understanding
the role of natural killer (NK) cells in disease pathogenesis
Viral infections are implicated in a wide variety of
diseases. Our lab is principally interested in identifying regulatory
mechanisms that govern the immune response to infection, and understanding how
these factors contribute to pathogen elimination, tissue damage, and resolution
of inflammation. Our investigations usually originate in murine models of
infection, wherein specific immune elements can be manipulated in an intact
organism during acute or persistent infection. Where possible we attempt to
translate the paradigms established in mice to human cells in culture. We
specialize in a wide variety of techniques that measure immune function,
including a number of flow cytometry-based analyses.
Our most recent work has uncovered a vital regulatory
role for natural killer (NK) cells in the pathogenesis of diseases associated
with virus infections in mice. This activity of NK cells prevented fatal
pathology associated with some viral inoculums by favoring functional
exhaustion of antiviral T cells. NK cell killing of activated CD4 T cells was
identified as a major mechanism contributing to regulation of virus-specific
CD8 T cell functionality in the context of persistent virus replication. We are
currently assessing the precise antigenic nature of the cells targeted by NK
cells during virus infection in order to determine pathways that could be
exploited to limit or augment this regulatory activity in therapy of human
diseases, including autoimmunity and chronic viral infections. Moreover, we are
exploring whether and how the immunoregulatory activity of NK cells contributes
to immune dysfunction in the elderly or to the efficacy of certain vaccine
regimens.